Intravenous drug abusers have become the largest source of heterosexual transmission of AIDS. Since their risk-taking behavior has been extremely resistant to change, it is imperative that we become more successful in the treatment of i.v. drug abuse if we are to focus on AIDS prevention. The currently proposed research investigates problems relevant to understanding and treating uncontrolled cocaine use, concentrating on the intravenous route of administration, and evaluating the behavioral mechanisms of action of a number of pharmacological agents proposed for the treatment of cocaine abuse. This is especially relevant since i.v. cocaine use may be even more likely than heroin to contribute to HIV infection. Minimal data exist on the relationship between cocaine-taking and maintenance on a variety of pharmaceutical substances proposed as possible treatment agents for cocaine abusers. This research will evaluate cocaine-taking behavior as well as its subjective effects, including "craving," and physiological effects before and during maintenance on carbamazepine, mazindol and sertraline, three currently proposed treatment agents. As newer agents are proposed, they, too, will be evaluated. Evaluations will be carried out under conditions in which subjects will have a broad range of behavioral options including cocaine- taking, and measures in shifts in choice of these options will be made. Since cocaine abstinence is the most desired treatment outcome, laboratory procedures in which the behavior of cocaine self-administration is specifically measured under conditions with some comparability to those outside of the laboratory show the most promise as a laboratory model for assessment of potential pharmacotherapeutic agents. Such a model would enable faster development of promising agents, reserving costlier and arduous double blind trials for those most potentially useful and as well, providing considerably more information about the behavioral mechanisms of action of the compounds being tested because of the careful laboratory control possible.